Langerhans Cell Density in Cervical Intraepithelial Neoplasia Associated With Human Papillomavirus Infection in HIV-Infected and HIV-Noninfected Brazilian Women
ABSTRACT Local immunity plays an important role in the cervical defense mechanisms that prevent the development of cervical intraepithelial neoplasia. The objective of this study was to determine the involvement of local immunity by evaluating Langerhans cell (LC) density in cervical biopsies of human immunodeficiency virus (HIV)-positive and HIV-negative women.
A cross-sectional study was developed by including HIV-positive and HIV-negative women. All patients presented human papillomavirus DNA from the uterine cervix, which was detected by polymerase chain reaction or hybrid capture II. Cervical biopsies were assessed for LC density and cervical intraepithelial neoplasia. Langerhans cells were identified by immunohistochemistry using anti-CD1a and anti-S100 antibodies. Associations among cervical LC density, the type of cervical lesion, CD4 lymphocyte count, and HIV viral load were analyzed using logistic regression (SPSS, version 12.0).
Seventy-seven women (40 seropositive and 37 seronegative) were enrolled. The mean ± SD LC density identified with the anti-CD1a antibody was 0.80 ± 0.7 cells versus 2.6 ± 1.6 cells (P < 0.0001), whereas the mean ± SD LC density identified by the anti-S100 antibody was 1.3 ± 1.0 cells versus 3.6 ± 1.7 cells (P < 0.0001) among the HIV-positive and HIV-negative women, respectively. There were no associations between LC density and HIV viral load, CD4 lymphocyte count, or human papillomavirus genotype (P > 0.05). In a logistic regression model, HIV infection was the only factor independently associated with a decrease in LC density.
Human immunodeficiency virus infection was found to be an independent factor that explains the decrease in local immunity in the uterine cervix, which could allow the development of cervical lesions. This effect was not associated with CD4 lymphocyte count or HIV viral load.
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ABSTRACT: Decreased numbers of Langerhans cells (LCs) in the cervix of human immunodeficiency virus (HIV)-infected women are believed to contribute to the progression of human papilloma virus (HPV)-related squamous intraepithelial lesions. However, this impairment of local immunity has not been well studied in the vulva. The objective of this study was to compare the S100+ LC density in high-grade vulvar intraepithelial neoplasia (VIN) in HIV-positive and HIV-negative women. HIV-positive and HIV-negative patients with high-grade VIN, 48 (55%) and 40 (45%), respectively, were identified by retrospective chart review. Smoking status of patients was noted. The mean LC count per high-power field (HPF) was determined using S100 immunohistochemical staining. In situ hybridization was performed to detect HPV DNA types 16 and 18. Mean S100+ LC counts for HIV-positive and HIV-negative patients were 5.82 and 9.86 per HPF, respectively (p = 0.0026). LC counts in HIV-positive and HIV-negative patients were compared between smoking and nonsmoking groups (HIV-positive p = 0.4812, HIV-negative p = 0.2821). HIV-positive patients with high-grade VIN had significantly lower LC counts compared with HIV-negative patients. This suggests that local vulvar immunity as evaluated by S100+ LCs is impaired in HIV-positive women, possibly contributing to the progression of HPV-related vulvar lesions.Journal of Cutaneous Pathology 08/2007; 34(7):565-70. DOI:10.1111/j.1600-0560.2006.00663.x · 1.56 Impact Factor
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ABSTRACT: Langerhans cells play a pivotal role as professional antigens presenting cells in cervical epithelium, thus changes in their density or/and function may profoundly influence the proper activation of the afferent arm of immune response in cases of HPV-related intraepithelial lesions. Assessment of intraepithelial Langerhans cell count changes in CIN I/CIN II after human recombinant interferon gamma (IFNgamma) application and correlation with clinical outcome. The present study is a part of prospective trial on IFNgamma application in the treatment of CIN I/CINII associated with high-risk HPV infection. Seventeen subjects underwent uniform IFNgamma treatment (four intracervical injections in a two-day interval for a total dose of 6,000,000 IU). Langerhans cells were stained within cervical punch biopsy specimens with the use of polyclonal anti-S-100 antibody according to the three-step indirect peroxidase protocol, and their mean count calculated for the following groups: before IFNgamma treatment launching, immediately after completion of the treatment, and after two months of follow-up. The analysis revealed a rapid and significant increase in Lagerhans' cell count immediately after treatment completion (21.17/mm2 and 25.94/mm2, respectively, at p = 0.019) which further increased in the group of complete response (in 9 subjects; 32.22/mm2). After transient elevation of the Langerhans' cell count it returned to a level even lower than initially in the non-responder group (4 subjects; 20.25/mm2). Our data strongly support the observation from static studies suggesting that regression of HPV-related cervical lesions is associated with increased density of epithelial Langerhans cells.European journal of gynaecological oncology 01/2005; 26(3):294-8. · 0.60 Impact Factor
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ABSTRACT: Although human papillomavirus (HPV) DNA is detected in the majority of cervical cancers and their precursors (squamous intraepithelial lesions; SIL), the persistence or progression of cervical lesions could be associated with quantitative and functional alterations of dendritic/Langerhans cells (DC/LC). As LC abnormalities have been associated with a decreased expression of macrophage inflammatory protein 3alpha (MIP3alpha) in cervical SIL, we tested the effect of exogenous MIP3alpha on the migration of LC in a (pre)neoplastic epithelium formed in vitro. By using a Boyden chamber assay, we first showed that the migratory capacity of LC generated in vitro is significantly increased in the presence of MIP3alpha compared to control medium. We next demonstrated that MIP3alpha is able to increase the 3D infiltration of LC in organotypic cultures of HPV-transformed keratinocytes. This property to stimulate LC migration was not altered after inclusion of MIP3alpha in a bioadhesive polycarbophil gel. Moreover, the function of DC to exert cytostatic effects and to present alloantigens was not altered in the presence of MIP3alpha.Cancer Immunology and Immunotherapy 08/2007; 56(7):1087-96. DOI:10.1007/s00262-006-0255-2 · 3.94 Impact Factor